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1fv0

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Revision as of 15:02, 10 September 2015

FIRST STRUCTURAL EVIDENCE OF THE INHIBITION OF PHOSPHOLIPASE A2 BY ARISTOLOCHIC ACID: CRYSTAL STRUCTURE OF A COMPLEX FORMED BETWEEN PHOSPHOLIPASE A2 AND ARISTOLOCHIC ACID

Structural highlights

1fv0 is a 2 chain structure with sequence from Daboia pulchella. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	1fe7, 1cl5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[PA2B8_DABRR] Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

This is the first structural observation of a plant product showing high affinity for phospholipase A(2) and regulating the synthesis of arachidonic acid, an intermediate in the production of prostaglandins. The crystal structure of a complex formed between Vipera russelli phospholipase A(2) and a plant alkaloid aristolochic acid has been determined and refined to 1.7 A resolution. The structure contains two crystallographically independent molecules of phospholipase A(2) in the form of an asymmetric dimer with one molecule of aristolochic acid bound to one of them specifically. The most significant differences introduced by asymmetric molecular association in the structures of two molecules pertain to the conformations of their calcium binding loops, beta-wings, and the C-terminal regions. These differences are associated with a unique conformational behavior of Trp(31). Trp(31) is located at the entrance of the characteristic hydrophobic channel which works as a passage to the active site residues in the enzyme. In the case of molecule A, Trp(31) is found at the interface of two molecules and it forms a number of hydrophobic interactions with the residues of molecule B. Consequently, it is pulled outwardly, leaving the mouth of the hydrophobic channel wide open. On the other hand, Trp(31) in molecule B is exposed to the surface and moves inwardly due to the polar environment on the molecular surface, thus narrowing the opening of the hydrophobic channel. As a result, the aristolochic acid is bound to molecule A only while the binding site of molecule B is empty. It is noteworthy that the most critical interactions in the binding of aristolochic acid are provided by its OH group which forms two hydrogen bonds, one each with His(48) and Asp(49).

Structural basis of phospholipase A2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 A crystal structure.,Chandra V, Jasti J, Kaur P, Srinivasan A, Betzel Ch, Singh TP Biochemistry. 2002 Sep 10;41(36):10914-9. PMID:12206661^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Faure G, Gowda VT, Maroun RC. Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics. BMC Struct Biol. 2007 Dec 6;7:82. PMID:18062812 doi:http://dx.doi.org/10.1186/1472-6807-7-82
↑ Kasturi S, Rudrammaji LM, Gowda TV. Antibodies to a phospholipase A2 from Vipera russelli selectively neutralize venom neurotoxicity. Immunology. 1990 Jun;70(2):175-80. PMID:2115497
↑ Tsai IH, Lu PJ, Su JC. Two types of Russell's viper revealed by variation in phospholipases A2 from venom of the subspecies. Toxicon. 1996 Jan;34(1):99-109. PMID:8835338
↑ Chandra V, Jasti J, Kaur P, Srinivasan A, Betzel Ch, Singh TP. Structural basis of phospholipase A2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 A crystal structure. Biochemistry. 2002 Sep 10;41(36):10914-9. PMID:12206661

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fv0"

@@ Line 2: / Line 2: @@
 <StructureSection load='1fv0' size='340' side='right' caption='[[1fv0]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1fv0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Daboia_russellii_pulchella Daboia russellii pulchella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FV0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FV0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1fv0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Daboia_pulchella Daboia pulchella]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FV0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FV0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AR:9-HYDROXY+ARISTOLOCHIC+ACID'>9AR</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fe7|1fe7]], [[1cl5|1cl5]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fv0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1fv0 RCSB], [http://www.ebi.ac.uk/pdbsum/1fv0 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fv0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fv0 OCA], [http://pdbe.org/1fv0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fv0 RCSB], [http://www.ebi.ac.uk/pdbsum/1fv0 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PA28_DABRP PA28_DABRP]] Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:8835338</ref> <ref>PMID:2115497</ref> <ref>PMID:18062812</ref>
+[[http://www.uniprot.org/uniprot/PA2B8_DABRR PA2B8_DABRR]] Snake venom phospholipase A2 (PLA2) that shows weak neurotoxicity and medium anticoagulant effects by binding to factor Xa (F10) and inhibiting the prothrombinase activity (IC(50) is 130 nM) (PubMed:18062812). It also damages vital organs such as lung, liver and kidney, displays edema-inducing activities when injected into the foot pads of mice and induces necrosis of muscle cells when injected into the thigh muscle. Has a low enzymatic activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.<ref>PMID:18062812</ref> <ref>PMID:2115497</ref> <ref>PMID:8835338</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1fv0" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Daboia russellii pulchella]]
+[[Category: Daboia pulchella]]
 [[Category: Betzel, C]]
 [[Category: Chandra, V]]

1fv0

From Proteopedia

Revision as of 15:02, 10 September 2015

FIRST STRUCTURAL EVIDENCE OF THE INHIBITION OF PHOSPHOLIPASE A2 BY ARISTOLOCHIC ACID: CRYSTAL STRUCTURE OF A COMPLEX FORMED BETWEEN PHOSPHOLIPASE A2 AND ARISTOLOCHIC ACID

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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